scholarly journals Bortezomib plus dexamethasone induction followed by autologous stem cell transplantation in multiple myeloma: A study from India

2016 ◽  
Vol 7 (4) ◽  
pp. 44-48
Author(s):  
Jeevan Kumar ◽  
Sachin Minhas ◽  
Kamini Khillan ◽  
Manorama Bhargava ◽  
Shyam Aggarwal
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Response Rates ◽  
Novel Agents ◽  
High Dose ◽  
Newly Diagnosed

Background: The use of novel agents for induction prior to autologous stem cell transplantation (ASCT) has considerably improved the complete response (CR) rate in multiple myeloma (MM) patients. There are very few studies from the developing countries on the use of novel agents followed by ASCT.Aims and Objectives: The current study was aimed for retrospective evaluation of the efficacy and response rates of induction with bortezomib (Velcade) plus dexamethasone (VD regimen) followed by ASCT in Indian patients.Materials and Methods: Ten patients with newly diagnosed, symptomatic MM who had received four cycles of VD induction before stem cell collection were evaluated. High dose melphalan was given for conditioning followed by stem cell transfusion. Thalidomide or lenalidomide was used as post-transplantation maintenance treatment.Results: Post VD induction, the overall response rate (ORR) was 90% including 20% CR, 40% very good partial response (VGPR), and 30% partial response (PR). Post ASCT, the ORR was 100%, including 80% CR and 20% VGPR. The 5-year overall survival and progression free survival rates were 65.6% and 57.1%, respectively.Conclusions: The VD induction regimen was effective and well tolerated in this retrospective analysis of Indian patients with newly diagnosed MM. It significantly improved the post-induction and post-transplant response rates without affecting stem cell collection.Asian Journal of Medical Sciences Vol.7(4) 2016 44-48 

Sequential VAD (Vincristine, Adriamycin, Dexamethasone) and VTD (VELCADE®, Thalidomide, Dexamethasone) Induction Followed by High-Dose Therapy with Autologous Stem Cell Transplantation and Maintenance Treatment with VELCADE for Newly Diagnosed Multiple Myeloma: Interim Results of Phase II Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 952-952 ◽  
Author(s):  
Sung-Soo Yoon ◽  
Hye Jin Kim ◽  
Dong Soon Lee ◽  
Hyeon Seok Eom ◽  
Jun Ho Jang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Maintenance Treatment ◽  
Response Rate ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Newly Diagnosed

Abstract Introduction Effective reduction of myeloma before autologous stem cell transplantation (ASCT) prolongs survival in multiple myeloma patients. Recently, incorporation of novel agents resulted in improved response rate and reduced side effect in newly diagnosed multiple myeloma. Method: Patients are planned to receive 2 cycles of VAD (vincristine 0.4mg D1-4, adriamycin 9mg/m2 D1-4, dexamethasone 40mg D1-4, 9–12 every 3 weeks), and VTD (bortezomib 1.3mg/m2 D1, 4, 8, 11, thalidomide 100mg daily, dexamethasone 40mg D1-4, 9–12 every 3 weeks). High dose melphalan (200mg/m2) is used as a conditioning regimen for ASCT. Bortezomib (1.3mg/m2) as a maintenance treatment is administered weekly x 4 times every 6 weeks for 4 cycles after ASCT. Response was assessed by EBMT criteria, with additional category of nCR. Adverse events were graded by the NCI-CTCAE, Version 3.0. Result: At this interim analysis, 60 patients have been entered into the ongoing trial, and efficacy could be assessed in 53 patients. After 2 cycles of VAD, response rate was 70%. After VTD, two patients showed further improvement with additional CR, and an overall response was 97% with 14% CR. Especially, patients with poor prognostic cytogenetics (n=6) all responded after VTD. So far, autologous stem cells were successfully collected in all 28 patients with a median CD34+ count of 7.8 x 106/kg (range, 2.17–44.7 x 106/kg). In 24 patients who underwent autologous stem cell transplantation, five patients gained additional CR. There was no progression in patients completed bortezomib maintenance (n=9, CR 77%). The median follow-up duration was 6 months, median time to response was 1.4 months, and median overall survival was not reached. Grade 3,4 hematologic toxicity was more frequently observed after VAD than VTD (anemia 15.8%, 4.6%, neutropenia 7.9%, 3.5%), and incidence of grade 2,3 peripheral neuropathy was low (VAD 3.5%, VTD 7%). Conclusion: Sequential VAD and VTD induction therapy in newly diagnosed multiple myeloma was highly effective, even in patients with poor prognostic cytogenetics, and did not prejudice stem cell collection. VTD could have contributed to increased RR and minimized side effects. An updated results will be presented at the ASH meeting. *Protocol Number: KMM51-NCT00378755.

Autologous Stem Cell Transplantation—An Important Step Toward Improving Survival in Multiple Myeloma

2010 ◽  
Vol 06 ◽  
pp. 24
Author(s):  
Ajay Gupta ◽  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
Response Rates ◽  
Major Advance

Conventional chemotherapy has been used in the treatment of multiple myeloma; however, the development of autologous stem cell transplantation (ASCT) represented a major advance in the therapy. Complete response (CR) rates of 40–45% were seen and this translated into improvements in progression-free survival (PFS) and overall survival (OS) in some studies. As a result, ASCT is the standard of care in eligible patients and can be carried out with low treatment-related mortality. The introduction of newer agents such as thalidomide, lenalidomide, bortezomib, and liposomal doxorubicin into induction regimens has resulted in higher CR rates, very good partial response rates (VGPR), and improvements in the ease of administration. These drugs have also proved useful in patients with adverse cytogenetics. Recent trials suggest that this has translated into improvements in response rates post-ASCT. There is a suggestion that patients achieving CR/near-CR (nCR) or VGPR after induction therapy should be placed on maintenance and ASCT could then be used as a treatment strategy at relapse; however, all of these trends await confirmation from further trials. Tandem transplants have been used to augment the results obtained with ASCT and have demonstrated their utility in patients who achieved only a partial response or stable disease in response to the first transplant and patients with adverse cytogenetics. Incorporation of bortezomib along with melphalan into the conditioning regimen has also been tried. It is hoped that recent advances in therapy will contribute greatly to improved survival.

High Dose Therapy with Autologous Stem Cell Transplantation Vs Standard Dose Chemotherapy In Multiple Myeloma: A Meta-Analysis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3559-3559
Author(s):  
Florian Faußner ◽  
Markus Pfirrmann ◽  
Wolfram Dempke
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Additional Data ◽  
Standard Dose ◽  
High Dose ◽  
Newly Diagnosed

Abstract Abstract 3559 Introduction. Myeloablative high dose chemotherapy (HDT) followed by single autologous stem cell transplantation is currently the standard treatment for patients younger than 65 years in newly diagnosed multiple myeloma (MM). Several randomized controlled trials (RCTs) comparing HDT with standard dose therapy (SDT) have shown some benefit in overall survival (OS) and progression free survival (PFS), whereas other RCTs did not confirm this finding. Koreth et al. (2007) performed a metaanalysis summarizing the existing data of the RCTs including 2,411 patients. These authors found a significant superiority for HDT in PFS but not in OS. Since a number of new studies have been published recently, we attempted to re-analyze the current data in terms of the endpoints OS and PFS. Methods. We searched PubMed, Embase, abstracts of former ASH meetings and ClinicalTrials.gov as well as bibliographies of included trials and recent reviews from september 2009 until may, 20th 2010. Amongst the 3,484 results in this search we identified 10 RCTs comparing HDT with SDT on an intent-to-treat-basis. Treatment characeristics and outcomes of OS and PFS were calculated using R. Furthermore, we tested for statistical heterogenity, publication bias and performed subgroup analyses. Results. 9 RCTs including 2,600 patients were fully analyzed. Patients undergoing HDT with stem cell transplantation did have significant PFS benefit (Hazard Ratio 0.73; 95% conficence intervall 0.56–0.95; P=0.02) but not OS benefit (HR 0.90; 95% CI 0.74–1.10; P=0.32) compared to patients undergoing SDT. Additional data from ongoing clinical trials are expected, thus updated results at the meeting including 10 RCTs with about 3,400 patients will be presented. Conclusion. Although there is only a trend to OS benefit with HDT, it is currently still the first line treatment. Additional data from ongoing clinical trials and new studies using novel agents like thalidomide, lenalidomide and bortezomib are egerly warrented to finally evaluate the role of HDT in the treatment management of patients with newly diagnosed MM. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Ixazomib as Postinduction Maintenance for Patients With Newly Diagnosed Multiple Myeloma Not Undergoing Autologous Stem Cell Transplantation: The Phase III TOURMALINE-MM4 Trial

2020 ◽  
Vol 38 (34) ◽  
pp. 4030-4041
Author(s):  
Meletios A. Dimopoulos ◽  
Ivan Špička ◽  
Hang Quach ◽  
Albert Oriol ◽  
Roman Hájek ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Primary Endpoint ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
To Receive

PURPOSE Maintenance therapy prolongs progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) not undergoing autologous stem cell transplantation (ASCT) but has generally been limited to immunomodulatory agents. Other options that complement the induction regimen with favorable toxicity are needed. PATIENTS AND METHODS The phase III, double-blind, placebo-controlled TOURMALINE-MM4 study randomly assigned (3:2) patients with NDMM not undergoing ASCT who achieved better than or equal to partial response after 6-12 months of standard induction therapy to receive the oral proteasome inhibitor (PI) ixazomib or placebo on days 1, 8, and 15 of 28-day cycles as maintenance for 24 months. The primary endpoint was PFS since time of randomization. RESULTS Patients were randomly assigned to receive ixazomib (n = 425) or placebo (n = 281). TOURMALINE-MM4 met its primary endpoint with a 34.1% reduction in risk of progression or death with ixazomib versus placebo (median PFS since randomization, 17.4 v 9.4 months; hazard ratio [HR], 0.659; 95% CI, 0.542 to 0.801; P < .001; median follow-up, 21.1 months). Ixazomib significantly benefitted patients who achieved complete or very good partial response postinduction (median PFS, 25.6 v 12.9 months; HR, 0.586; P < .001). With ixazomib versus placebo, 36.6% versus 23.2% of patients had grade ≥ 3 treatment-emergent adverse events (TEAEs); 12.9% versus 8.0% discontinued treatment because of TEAEs. Common any-grade TEAEs included nausea (26.8% v 8.0%), vomiting (24.2% v 4.3%), and diarrhea (23.2% v 12.3%). There was no increase in new primary malignancies (5.2% v 6.2%); rates of on-study deaths were 2.6% versus 2.2%. CONCLUSION Ixazomib maintenance prolongs PFS with no unexpected toxicity in patients with NDMM not undergoing ASCT. To our knowledge, this is the first PI demonstrated in a randomized clinical trial to have single-agent efficacy for maintenance and is the first oral PI option in this patient population.

Induction Therapy with Novel Agents Improves Relapse-Free Survival After Autologous Stem-Cell Transplantation in Multiple Myeloma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4494-4494
Author(s):  
Sandra Eder ◽  
Wolfgang Lamm ◽  
Michaela Gruber ◽  
Beatrice Schauer ◽  
Jutta Ackermann ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Initial Treatment ◽  
Novel Agents ◽  
High Dose ◽  
Relapse Free Survival ◽  
Free Survival

Abstract Abstract 4494 Introduction: Multiple myeloma (MM) is still an incurable disease. Initial treatment depends on age, risk stratification and co-morbidities. High-dose therapy followed by autologous stem-cell transplantation (ASCT) is the standard of care in transplant eligible patients. In recent years, novel agents became a promising role in newly diagnosed, relapsed myeloma as well as in maintenance treatment. Bortezomib, a proteasome inhibitor, and thalidomide or lenalidomide, immunomodulatory agents have been found to be superior to chemotherapy regimens. Methods: 121 adult patients (50 female, 71 male) with a median age of 53.5 years at diagnosis underwent autologous stem-cell transplantation at the Medical University of Vienna between June 1985 and September 2010. Median age at ASCT was 57.4 years. 46 patients received novel therapeutic agents, such as VDT (bortezomib, dexamethasone, thalidomide), Rd (lenalidomide, low dose dexamethasone) and VD (bortezomib, dexamethasone), whereas 75 patients were treated on the basis of chemotherapy schedules, e.g. VAD-based (vincristine, doxorubicin, dexamethasone). Results: Progression-free survival (PFS) after ASCT was 7.9 months (6,4 – 9,3, 95% CI) after treatment with chemotherapy, whereas it was increased to 21,6 months (5 – 38,1, 95% CI) after initial treatment with either bortezomib and/or thalidomide/lenalidomide (p= 0.001). Post-induction VGPR or better was superior with new agents compared to chemotherapy, 34,1% versus 11,9%, respectively. Post-transplant VGPR or better was as high as 68% after initial therapy with novel agents prior to transplant, whereas VGPR or better was reached in 48.6% in patients receiving chemotherapy. Conclusion: Novel agents significantly prolong relapse-free survival in patients eligible for autologous stem-cell transplantation. Previous studies showed improved remission duration with thalidomide or lenalidomide maintenance after ASCT. The data of maintenance therapy after ASCT at our department will be presented at the meeting. Disclosures: No relevant conflicts of interest to declare.

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